RhoA/Rho kinase-mediated Ca2+ sensitization in the contraction of human prostate

Ryosuke Takahashi, Junji Nishimura, Narihito Seki, Takakazu Yunoki, Toshihisa Tomoda, Hideo Kanaide, Seiji Naito

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Abstract

Aims: The contractile mechanisms of prostatic smooth muscle have been extensively investigated at the receptor level. However, the intracellular mechanisms have not yet been fully elucidated, especially in human tissue. In the present study, we examined the functional role of RhoA/Rho kinase (ROCK), one of the major intracellular molecules involved in smooth muscle contraction, in the contraction of the human prostate. Methods: Ring preparations made of cultured human prostatic stromal cells (CHPSCs) or fresh human prostatic tissue was used for an isometric tension study. Gene transfer using baculovirus vector and α-toxin permeabilized preparations were also used. Results: RhoA, ROCK I and ROCK II proteins were all expressed in CHPSCs and fresh human prostatic tissue. In CHPSCs ring preparations, the contraction induced by endothelin (ET)-1 was enhanced by over-expression of RhoA and inhibited by ROCK inhibitor. In α-toxin permeabilized preparations, ET-1 or GTP-γS induced an additional contraction at a constant [Ca2+]i, that was inhibited by ROCK inhibitor. In fresh human prostatic tissue, norepinephrine (NE)-induced contraction was inhibited by ROCK inhibitor at a constant [Ca 2+]i in α-toxin permeabilized preparations. Conclusions: These results suggested that RhoA/ROCK-mediated Ca2+ sensitization is likely involved in the contraction of the human prostate. The antagonisms of this pathway may thus be useful as an alternative target in the treatment of benign prostatic hyperplasia (BPH).

Original languageEnglish
Pages (from-to)547-551
Number of pages5
JournalNeurourology and Urodynamics
Volume26
Issue number4
DOIs
Publication statusPublished - Jul 12 2007

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All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Urology

Cite this

Takahashi, R., Nishimura, J., Seki, N., Yunoki, T., Tomoda, T., Kanaide, H., & Naito, S. (2007). RhoA/Rho kinase-mediated Ca2+ sensitization in the contraction of human prostate. Neurourology and Urodynamics, 26(4), 547-551. https://doi.org/10.1002/nau.20365